Bacterial Meningitis is still a relatively common disease worldwide. Despite the introduction of antibiotics, the morbidity and mortality rates have not improved in 30 years. We will examine several aspects of the pathogenesis of this disease by various in vitro and experimental animal model in vivo techniques in an attempt to improve the results of treatment. The effect(s) of meningitis on the blood-brain barrier (BBB) is unclear. We will determine the effect of meningitis and cerebrospinal fluid (CSF) inflammation on the transport functions (hexoses, antibiotics) and morphology of isolated cerebral capillaries in vitro and on leukocyte emigration (fluorescein or radiolabeled) from the pial microcirculation under direct observation in vivo. We will correlate these results with studies on the functional integrity of the BBB and observation by light microscopy, scanning and transmission electron microscopy. The bacterial route of invasion into the CSF is not known. We will determine bacterial adhesion to BBB components (including cerebral microvessel endothelial cells), and the effect(s) of CSF inflammation and BBB perturbation on bacterial entry into the CSF. The influence of meningitis on basic neurophysiologic parameters is poorly understood. We will define the effect of meningitis and CSF inflammatory substances on cerebral blood flow and its regulation, cerebral metabolic rate for oxygen, and lactate production by interrelated techniques.